摘要目的:探讨双胎早产儿出生顺序与其早期神经发育结局的关联。方法:回顾性队列研究，以2020年1月至2024年12月重庆医科大学附属儿童医院新生儿科收治的2 251例双胎新生儿为研究对象，收集并分析包括一般资料、围生期结局、住院期间和早期即校正胎龄≤4月龄神经发育评估指标在内的临床资料。神经发育评估包括颅脑超声、振幅整合脑电图（aEEG）及婴儿运动表现测试（TIMP）等。每对双胎早产儿根据出生顺序分为先出生组和后出生组，并按绒毛膜性（单绒、双绒）、出生胎龄（28~31、32~33、34~36周）及出生方式（自然出生、剖宫产出生）进行亚组分析，采用配对 t检验、Wilcoxon符号秩和检验、McNemar检验或精确McNemar检验进行组间比较；进一步构建双胎对聚类的多因素回归模型，评估双胎早产儿纳入分析，出生顺序与其早期神经发育结局的关联。 结果:225对双胎早产儿纳入分析，出生胎龄为（33.9±1.8）周，先、后出生组出生体重分别为（2 002±389）及（1 956±363）g，男性占比分别为52.9%（119/225）及49.8%（112/225）。后出生组第1分钟 Apgar评分 <7分比例、呼吸衰竭发生率均高于先出生组（均 P<0.05），血气pH及碱剩余值均低于先出生组（均 P<0.05）。先、后出生组脑室扩大及脑室周围-脑室内出血检出率差异均无统计学意义［8.6%（19/221）比12.2%（27/221），23.1%（51/221）比19.5%（43/221），均 P>0.05］。后出生组更高aEEG成熟度评分的相对概率降低［累积 OR=0.48，95% CI 0.33~0.72， P<0.001］。住院期间先、后出生组TIMP Z值差差异无统计学意义（ P=0.537），随访期间（校正年龄≤4月龄）随时间的变化趋势无统计学意义（ β=0.01，95% CI -0.02~0.04， P=0.637）。亚组分析提示后出生组在单绒毛膜亚组（累积 OR=0.34，95% CI 0.14~0.79， P=0.013）、双绒毛膜亚组（累积 OR=0.52，95% CI 0.33~0.82， P=0.005）、出生胎龄32~33周亚组（累积 OR=0.40，95% CI 0.19~0.87， P=0.021）、出生胎龄34~36周亚组（累积 OR=0.56，95% CI 0.34~0.94， P=0.027）及剖宫产出生亚组（累积 OR=0.49，95% CI 0.32~0.73， P=0.001）获得更高aEEG校正总分的相对概率均低于先出生组；而在出生胎龄28~31周及自然出生亚组差异均无统计学意义（均 P>0.05）；各亚组中先、后出生组脑室周围-脑室内出血检出率差异均无统计学意义（均 P>0.05）；脑室扩大检出率经校正后差异均无统计学意义（均 q>0.05）。自然出生亚组中，住院期间TIMP Z值差与0相比经校正后差异无统计学意义（ q=0.269）。随访期间随时间的变化趋势均无统计学意义（均 P>0.05）。 结论:出生顺序与双胎早产儿早期脑功能成熟度相关。应重视早产、多胎等高危儿脑电监测与神经发育随访，以便早期识别、干预，降低脑功能发育异常的风险。

abstractsObjective:To explore the association between birth order and early neurodevelopmental outcomes in preterm twin infants.Methods:A retrospective cohort study was conducted on 2 251 of twin neonates admitted to the Department of Neonatology, Children′s Hospital of Chongqing Medical University, from January 2020 to December 2024. Clinical data including general characteristics, perinatal outcomes, and neurodevelopmental assessments (cranial ultrasonography, amplitude-integrated electroencephalography (aEEG) and the test of infant motor performance (TIMP) during hospitalization and follow-up up to corrected age ≤4 months, were collected and analyzed. Each pair of preterm twins was grouped into first-born and second-born groups according to birth order. Subgroup analyses were performed according to chorionicity (monochorionic, dichorionic), gestational age at birth (28-31, 32-33, 34-36 weeks), and mode of delivery (vaginal delivery, cesarean section). Paired t test, Wilcoxon signed-rank test, McNemar test or exact McNemar test were used for paired comparisons, and a multivariable regression model accounting for within-pair of twins clustering was further constructed to evaluate the association between birth order and early neurodevelopmental outcomes. Results:A total of 225 twin pairs were enrolled, with a gestational age of (33.9±1.8) weeks. Birth weight was (2 002±389) g in first-born twins and (1 956±363) g in second-born twins; the proportion of males was 52.9% (119/225) and 49.8% (112/225), respectively. The second-born group had higher rates of the first minute Apgar score <7 and respiratory failure compared with the first-born group (both P<0.05), along with lower blood-gas pH and base excess (both P<0.05). There were no differences between the first-born and second-born groups in ventriculomegaly (8.6% (19/221) vs. 12.2% (27/221)) or periventricular-intraventricular hemorrhage (23.1% (51/221) vs. 19.5% (43/221)) (both P>0.05). The second-born twins had lower odds of achieving higher aEEG Burdjalov scores (cumulative OR=0.48, 95% CI 0.33-0.72, P<0.001). No significant deviation of the within-pair TIMP Z-score difference from 0 was observed during hospitalization ( P=0.537). In longitudinal analysis (corrected age ≤4 month), the time slope had no difference ( β=0.01,95% CI -0.02-0.04, P=0.637). Subgroup analyses showed that lower odds of higher Burdjalov scores for second-borns remained statistical difference in monochorionic twins (cumulative OR=0.34,95% CI 0.14-0.79, P=0.013), dichorionic twins (cumulative OR=0.52,95% CI 0.33-0.82, P=0.005), the gestational age of 32-33 week at birth subgroup (cumulative OR=0.40,95% CI 0.19-0.87, P=0.021), the gestational age 34-36 weeks at birth subgroup (cumulative OR=0.56,95% CI 0.34-0.94, P=0.027), and the cesarean section subgroup (cumulative OR=0.49,95% CI 0.32-0.73, P=0.001), whereas no statistical difference were observed in the gestational age of 28-31 weeks at birth or the birth via vaginal delivery subgroup (all P>0.05). Across all subgroups, no statistical difference was found in periventricular-intraventricular hemorrhage (all P>0.05), and in ventriculomegaly after correction (all q>0.05). In the birth via vaginal delivery subgroup, the difference in TIMP Z-scores compared to 0 had no statistical difference after correction ( q=0.269). During the follow-up period, there were no trends in the change of TIMP Z-scores over time (all P>0.05). Conclusions:Birth order was associated with brain functional maturity among preterm twins. Enhanced aEEG monitoring and neurodevelopmental follow-up are recommended for high-risk newborns, including preterm and multiple births, to facilitate early detection and intervention, thus reducing the risk of impaired brain development.